Abnormal cells and acellular organisms are known to selectively absorb certain dyes (photosensitive materials) delivered to a treatment site to a more pronounced extent than surrounding tissue. Once presensitized, abnormal cells or acellular organisms can be destroyed by irradiation with light of an appropriate wavelength corresponding to an absorbing wavelength of the photosensitive material, with minimal damage to surrounding normal tissue. This procedure, which is known as photodynamic therapy (PDT), has been clinically used to treat metastatic breast cancer, bladder cancer, head and neck cancers, esophageal cancer, lung cancer, and other types of malignant tumors, actinic keritosis, and macular degeneration.
U.S. Pat. No. 5,676,959 to Heitz et al., purportedly discloses an ingestible phototoxic insecticidal composition including a photoactive dye, an attractant compound and/or feeding stimulant, and an adjuvant, whereby the adjuvant interacts with the photoactive dye and insect gastrointestinal (GI) tract to facilitate transport of the phototoxic insecticide across the GI tract. The use of an adjuvant to facilitate pharmaceutical uptake via GI tract absorption is known in the art. Unlike the surface acting agents of the Applicant's present invention, these adjuvants do not produce a disorientation of a cell membrane so that the cell membrane no longer functions as an effective osmotic barrier.
The article “Inactivation of Gram-Negative Bacteria by Photosensitized Porphyrins” by Nitzan, et al., published in Photochemistry and Photobiology, Vol. 55, No. 1, pp. 89-96, 1992, purportedly discloses the use of polycationic agent polymyxin nonapeptide (PMNP) in association with a photoactive agent, deuteroporphyin (DP). PMNP is disclosed to disturb the outer membrane of a gram-negative bacteria so as to permit access of the DP to bind to the internal lipoprotein osmotic membrane of the bacterial cell. PMNP is disclosed to only disturb the outer membrane structure and not its function, and not cause metabolic leakage from the cells (or osmotic changes in the cell). Unlike the surface acting agent of the Applicant's present invention, PNMP does not produce a disorientation of a cell membrane so that the cell membrane no longer functions as an effective osmotic barrier. In the Applicant's present invention, the surface acting agent causes a disorientation of the cell membrane thereby compromising the effective osmotic membrane barrier and thus allowing the photosensitizer to diffuse through the compromised cell membrane into the cell.
U.S. Pat. No. 5,616,342, to Lyons, purportedly discloses an emulsion comprising a lipid, a poorly water-soluble photosensitizing compound, a surfactant, and a cosurfactant. Poorly water-soluble photosensitizers are disclosed to pose serious challenges to achieving suitable formulation for administration to the body. Lyons '342 discloses that surfactants facilitate the preparation of the emulsion by stabilizing the dispersed droplets of an oil-in-water emulsion, and that the use of surfactants in combination with poorly water-soluble pharmacologic compounds is known in the art. Unlike the surface acting agents of the Applicant's present invention, the surfactant in Lyons does not produce a disorientation of a cell membrane so that the cell membrane no longer functions as an effective osmotic barrier.
Many hospitalized patients, particularly patients in an Intensive Care Unit (“ICU”), must be fitted with endotracheal tubes to facilitate their respiration. An endotracheal tube is an elongate, semi-rigid lumen which is inserted into a patient's nose or throat and projects down into airflow communication with the patient's respiratory system. As such, the patient either directly, or with the aid of a respiratory unit, is able to breathe more effectively through the endotracheal tube. Endotracheal tubes may remain in place within a patient for an extended period of time, e.g. up to a 14 day period. Biofilm contamination of endotracheal tubes within intubated patients may lead to an increased rate of infection, particularly pneumonia. An effective apparatus and method of use for eradication of biofilm organism on endotracheal tubes of intubated patients is desired.
Occurrences of catheter related bloodstream infection (CRBSI) have increased in part as a result of the wide use of invasive medical devices, including intravascular catheters. CRBSI is one of the most common types of nosocomial bloodstream infection, a finding that has been attributed to the wide use of intravascular catheters in hospitalized patients. Recent interventions to control CRBSI include anticoagulant/antimicrobial lock, use of ionic silver at the insertion site, employment of an aseptic hub model, and antimicrobial impregnation of catheters.
Several factors pertaining to the pathogenesis of CRBSI have been identified. The skin and hub are the most common sources of colonization of percutaneous vascular catheters. For short-term, non-nontunneled, noncuffed catheters, the organisms migrate from the skin insertion site along the intercutaneous segment, eventually reaching the intravascular segment of the tip. For long-term catheters, the hub is a major source of colonization of the catheter lumen, which ultimately leads to bloodstream infections through luminal colonization of the intravascular segment.
The catheter surface is another factor relating to the pathogenesis of CRBSI. Organisms that adhere to the catheter surface maintain themselves by producing an “extracellular slime,” a substance rich in exopolysaccharides, often referred to as fibrous glycocalyx or microbial biofilm. Microorganisms bind to the surface of host proteins, such as fibrin and fibronectin, to produce biofilm. As described in more detail herein, the organisms embed themselves in the biofilm layer, often becoming more resistant to antimicrobial activity. The use of lumen flush solutions including a combination of antimicrobial agents as well as anti-coagulants is a known process. Another strategy has been to impregnate the surfaces of catheters with antimicrobial agents in order to prevent colonization and the formation of biofilm. An improved approach for prevention of intravascular catheter-related infections is desired.
A considerable amount of attention and study has been directed toward preventing colonization of bacterial and fungal organisms on the surfaces of orthopedic implants by the use of antimicrobial agents, such as antibiotics, bound to the surface of such devices. The objective of such attempts has been to produce a sufficient bacteriostatic or bactericidal action to prevent colonization. Various methods have previously been employed to coat the surfaces of medical devices with an antibiotic.
U.S. Pat. No. 4,442,133, invented by Greco et al., discloses a method to coat the surface of medical devices with antibiotics involving first coating the selected surfaces with benzalkonium chloride followed by ionic bonding of the antibiotic composition. Applicant incorporates by reference herein the teachings of U.S. Pat. No. 4,442,133.
U.S. Pat. No. 4,879,135, invented by Greco et al., discloses surface modification of surgical implants by binding of drugs which, after implantation, are slowly released. More particularly, the invention relates to improved surgical implants having sustained, localized delivery of pharmacological agents such as extended antibiotic activity or reduced thrombogenicity, and methods for producing same. The surface modification of surgical implants by the adhesion thereto of pharmacological agents for the purpose of minimizing infection and prosthesis rejection is well-known and has generated broad interest for some time. Applicant incorporates by reference herein the teachings of U.S. Pat. No. 4,879,135. Many different approaches have been taken including those disclosed in U.S. Pat. Nos. 4,563,485; 4,581,028; 5,707,366; and 4,612,337, each being incorporated by reference herein.
A biofilm is an accumulation of microorganisms including bacteria, fungi and viruses that are embedded in a polysaccharide matrix and adhere to solid biologic and non-biologic surfaces. Biofilms are medically important as they may account for a majority of microbial infections in the body. Biofilms account for many of the infections of the oral cavity, middle ear, indwelling catheters and tracheal and ventilator tubing. The National Institutes of Health estimates that the formation of biofilms on heart valves, hip and other prostheses, catheters, intrauterine devices, airway and water lines and contact lenses has become a $20 billion dollar health problem in the United States. A treatment apparatus and protocol for the reduction and/or eradication of biofilms is another aspect of the present invention.
Biofilms are remarkably resistant to treatment with conventional topical and intravenous antimicrobial agents. The Center for Biofilm Engineering at Montana State University has reported that biofilms may require 100 to 1,000 times the standard concentration of an antibiotic to control a biofilm infection. This is thought to be due to the antibiotic's inability to penetrate the polysaccharide coating of the biofilm. Even more concerning is that biofilms increase the opportunity for gene transfer due to the commingling of microorganisms. Such gene transfer may convert a previous avirulent commensal organism into a highly virulent and possibly antibiotic resistant organism.
Bacteria embedded within biofilms are also resistant to both immunological and non-specific defense mechanisms of the body. Bacterial contact with a solid surface triggers the expression of a panel of bacterial enzymes that cause the formation of polysaccharides that promote colonization and protection of the bacteria. The polysaccharide structure of biofilms is such that immune responses may be directed only at those antigens found on the outer surface of the biofilm and antibodies and other serum or salivary proteins often fail to penetrate into the biofilm. Also, phagocytes may be effectively prevented from engulfing a bacterium growing within a complex polysaccharide matrix attached to a solid surface.
Nosocomial pneumonia is the most prevalent infection in patients who are mechanically ventilated. It is the leading contributor to mortality in patients, accounting for 50% of deaths in patients with hospital acquired infections. The endotracheal tubes (ET) and tracheostomy tubes have long been recognized as a risk factor for nosocomial pneumonia since they bypass host defenses allowing bacteria direct access to the lungs. These tubes are commonly made of polyvinyl chloride, a surface on which local bacteria colonize rapidly to form an adhesive polysaccharide glycocalyx layer. This glycocalyx layer protects bacterial colonies from both natural and pharmacologic antibacterial agents, in effect increasing the virulence of the bacterial species in the intubated host. This phenomenon of biofilm formation has been demonstrated to occur on ET tubes and subsequent dislodgement of biofilm protected bacteria in the lungs by a suction catheter is considered to be a significant factor in the pathogenesis of nosocomial pneumonia. Indeed, in a study of biofilm formation in endotracheal tubes, microbial biofilm was identified by surface electron microscopy in 29 of 30 endotracheal tubes examined. Interestingly, there was no biofilm formation on the outer surface of the ET tube. Biofilm formed exclusively on the luminal surface of all tubes regardless of whether the patients had received broad spectrum antibiotics and was most prevalent around the side hole of the tip region. ET tubes obtained within 24 hours of placement showed large areas of surface activity with adherent bacteria in a diffuse pattern indicating initial colonization of the ET tube. The surface of tubes in place for longer periods had a profuse microbial biofilm. In some instances a large mass of matrix enclosed bacterial cells appeared to project from the confluent accretion on the luminal surface of the ET tube in such a manner that it could be dislodged readily and aspirated into the lower respiratory tract. Pseudomonas species, Staphylococcus aureus, and enteric aerobic bacteria including E. coli, were the most frequently isolated pathogens in the ET tubes in patients that did not receive broad spectrum antibiotics. These also are the pathogenic bacteria most commonly found in nosocomial pneumonia. In patients that received broad spectrum antibiotics yeast species and Streptococcus species were more common. Evaluations have been made into the relationship of biofilm formation in endotracheal tubes and distant colonization of the pulmonary tree. These evaluations have demonstrated that bacteria from the endotracheal tube biofilm were capable of being cultured from the moisture exchanger and the ventilator tubing up to 45 cm from the tip of the endotracheal tube. Furthermore they demonstrated that contamination of the tracheal tube biofilm with a patient's own gastrointestinal flora provides a mechanism for initial and repeated lung colonization and secondary pneumonia. These life threatening pulmonary infections are perpetuated by microbiological seeding from the tracheostomy and endotracheal tube biofilms and become difficult to treat due to the propensity of the biofilm microorganisms to develop antibiotic resistance. Biofilm contamination of endotracheal tubes within intubated patients may lead to infections or other complications as a result of biofilm organisms.
Catheters used for abdominal cavity tubing drainage bags and various connectors are also common sources of infection. In particular, a high percentage of patients who require long-term urinary catheters develop chronic urinary tract infections. Such patients are at risk of developing bacteremia or chronic pyelonephritis, condition of high morbidity and mortality. Many different medical articles may lead to infection when in contact with a body tissue or fluid. Exemplary of such articles are vascular access (arterial and venous) catheters, introducers, vascular grafts, urinary catheters and associated articles, such as drainage bags and connectors, and abdominal cavity drainage tubing, bags and connectors. A novel apparatus and method of infection prevention for such medical articles is particularly desired.
A variety of air filtration devices are known. A need exists, however, for an air filtration device which can neutralize biological threats associated with warfare. A need also exists for an improved air filtration device for building HVAC systems, particularly within hospitals and other care facilities. In such settings, an efficient system or process is needed for the removal of bacteria and fungi, such as aspergillus. Desired applications include a portable systems (mask form) and non-portable systems (a building or other structure filter system, or a vehicle interior air filter system). Known electromagnetic radiation pathogen destruction techniques have significant limitations. For example, UV and microwave destruction approaches may only reduce the bacteria count, and not eradicate the pathogens altogether. Furthermore, bacteria may become resistant to UW eradication over relatively short periods of time. Microwave destruction is through generation of severe heat. This modality would not be applicable as a portable biological weapon countermeasure. In comparison, photodynamic therapy antibacterial effects have demonstrated complete destruction and sterilization of highly concentrated bacterial species in vitro and therefore would appear to be superior to the above methods. An improved air filtration/decontamination device for efficiently and effectively eliminating harmful biological elements such as viruses, bacteria, fungus, etc., from the air is particularly desired.